trimethoprim--sulfamethoxazole-drug-combination and Encephalitis

Toxoplasmic encephalitis (TE) is an opportunistic infection of people with human immunodeficiency virus (HIV) or other causes of immunosuppression. Guideline-recommended treatments for TE are pyrimethamine and sulfadiazine (P-S) or pyrimethamine and clindamycin (P-C); however, a substantial price increase has limited access to pyrimethamine. Consequently, some centers have transitioned to trimethoprim-sulfamethoxazole (TMP-SMX), an inexpensive alternative treatment. We aimed to review the evidence on the efficacy and safety of pyrimethamine-containing therapies vs TMP-SMX.. We searched for and included randomized controlled trials (RCTs) and observational studies of TE treatments, regardless of HIV status. Data for each therapy were pooled by meta-analysis to assess the proportions of patients who experienced clinical and radiologic responses to treatment, all-cause mortality, and discontinuation due to toxicity. Sensitivity analyses limited to RCTs directly compared therapies.. We identified 6 RCTs/dose-escalation studies and 26 single-arm/observational studies. Identified studies included only persons with HIV, and most predated modern antiretroviral treatment. Pooled proportions of clinical and radiologic response and mortality were not significantly different between TMP-SMX and pyrimethamine-containing regimens (P > .05). Treatment discontinuation due to toxicity was significantly lower in TMP-SMX (7.3%; 95% confidence interval [CI], 4.7-11.4; I2 = 0.0%) vs P-S (30.5%; 95% CI, 27.1-34.2; I2 = 0.0%; P < .01) or P-C (13.7%; 95% CI, 9.8-18.8; I2 = 32.0%; P = .031). These results were consistent in analyses restricted to RCT data.. TMP-SMX appears to be as effective and safer than pyrimethamine-containing regimens for TE. These findings support modern RCTs comparing TMP-SMX to pyrimethamine-based therapies and a revisiting of the guidelines.

Topics: Encephalitis; HIV Infections; Humans; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

In a meta-analysis, we examined the efficacy of aerosolized pentamidine, trimethoprim-sulfamethoxazole, and dapsone or dapsone/pyrimethamine for the prevention of Pneumocystis carinii pneumonia and toxoplasma encephalitis in patients with HIV infection. Of 22 trials, 13 compared trimethoprim-sulfamethoxazole with aerosolized pentamidine, nine compared dapsone alone or in combination with pyrimethamine with aerosolized pentamidine, and eight compared trimethoprim-sulfamethoxazole with dapsone/pyrimethamine. In total, 1484 patients were treated with trimethoprim-sulfamethoxazole, 1548 patients with dapsone/pyrimethamine or dapsone, and 1800 patients with aerosolized pentamidine. For dapsone/pyrimethamine versus aerosolized pentamidine, the risk ratio for P. carinii pneumonia was 0.90 (95% confidence interval [CI], 0.71-1.15), and for toxoplasma encephalitis it was 0.72 (95% CI, 0.54-0.97). For trimethoprim-sulfamethoxazole versus aerosolized pentamidine, the risk ratio of P. carinii pneumonia was 0.59 (95% CI, 0.45-0.76), and for toxoplasma encephalitis it was 0.78 (95% CI, 0.55-1.11). For trimethoprim-sulfamethoxazole versus dapsone/pyrimethamine, the risk ratio of P. carinii pneumonia was 0.49 (95% CI, 0.26-0.92), and for toxoplasma encephalitis it was 1.17 (95% CI, 0.68-2.04). Although current evidence does not allow a definitive recommendation, administration of trimethoprim-sulfamethoxazole for prophylaxis of P. carinii pneumonia and toxoplasmosis in patients with HIV infection is consistent with the available data.

Topics: Administration, Inhalation; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Dapsone; Encephalitis; HIV Infections; Humans; Odds Ratio; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Randomized Controlled Trials as Topic; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Toxoplasmic encephalitis (TE) is the second most common AIDS-related opportunistic infection of the CNS. It occurs in 10%-50% of patients with AIDS who are seropositive for antibodies to Toxoplasma gondii and have CD4+ T lymphocyte counts of < 100/mm3. Primary toxoplasmic infection usually is acquired by ingestion of T. gondii oocysts from soil contaminated by cat feces or by ingestion of tissue cysts present in undercooked red meats. In patients with AIDS, TE probably results from the reactivation of Toxoplasma tissue cysts that remained latent after the primary infection. Detection of IgG antibodies to Toxoplasma indicates prior infection and the possible presence of tissue cysts and, thus, risk for developing TE. A regimen of trimethoprim-sulfamethoxazole or dapsone plus pyrimethamine with leucovorin is recommended for persons infected with the human immunodeficiency virus (HIV) and who are seropositive for IgG to Toxoplasma after their CD4+ T lymphocyte counts fall to < 100/mm3. HIV-infected persons who are seronegative for IgG to Toxoplasma should be counseled to protect themselves from primary toxoplasmic infection by eating only well-cooked meats and washing their hands after outdoor activities involving soil contact; if they have a cat, they should feed it only commercial or well-cooked foods, keep it indoors, and make sure that the litter box is changed daily. HIV-infected persons who are Toxoplasma seropositive may also be advised about these preventive behavioral practices.

Topics: AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Cats; Dapsone; Drug Therapy, Combination; Encephalitis; Humans; Incidence; Leucovorin; Pyrimethamine; Recurrence; Risk Factors; Toxoplasmosis, Animal; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; United States

The preferred therapeutic regimen for Toxoplasma encephalitis (TE) is a combination of pyrimethamine and sulfadiazine, and trimethoprim-sulfamethoxazole (TMP-SMX) plus azithromycin is the widespread alternative therapeutic regimen. The synergistic sulfonamides tablet contains TMP, sulfadiazine, and SMX and hypothetically could be used for TE treatment. This study aimed to compare the efficacy and safety of synergistic sulfonamides plus clindamycin (regimen B) with TMP-SMX plus azithromycin (regimen A) for the treatment of human immunodeficiency virus (HIV) associated TE.. This was an open-labeled, multi-center randomized controlled trial recruited from 11 centers. Each recruited patient was randomly assigned to receive regimen A or regimen B for at least 6 weeks. The overall response was evaluated by assessment of the clinical response of TE-associated clinical features and the radiological response of TE-associated radiological findings. The overall response rate, clinical response rate, radiological response rate, and adverse events were assessed at 2, 6, and 12 weeks. Death events were compared between the two regimens at 6, 12, and 24 weeks.. A total of 91 acquired immunodeficiency syndrome (AIDS)/TE patients were included in the final analysis (44 in regimen A vs . 47 in regimen B). The overall response rate, which refers to the combined clinical and radiological response, was 18.2% (8/44) for regimen A and 21.3% (10/47) for regimen B at week 6. The results of clinical response showed that, in comparison with regimen A, regimen B may perform better with regards to its effect on the relief of clinical manifestations (50.0% [22/44] vs . 70.2% [33/47], P = 0.049). However, no significant differences in radiological response, mortality events, and adverse events were found between the two regimens at week 6.. Synergistic sulfonamides plus clindamycin, as a novel treatment regimen, showed no significantly different efficacy and comparable safety in comparison with the TMP-SMX plus azithromycin regimen. In addition, the regimen containing synergistic sulfonamides may exhibit advantages in terms of clinical symptom alleviation.. ChiCTR.org.cn, ChiCTR1900021195.

Topics: Acquired Immunodeficiency Syndrome; Azithromycin; Clindamycin; Encephalitis; Humans; Sulfadiazine; Sulfanilamide; Sulfonamides; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Autoimmune encephalitis is a new spectrum of autoimmune disorders of the central nervous system (CNS), which are characterized by pathogenic autoantibodies against neuronal surface antigens. Clinical presentations range from acute to subacute encephalopathy with neurological and psychiatric symptoms, and life-threatening autonomic dysfunction in severe cases. There exist no approved therapies nor is data available from controlled clinical trials. Patients are usually treated with diverse combinations of immunotherapy. However, effect of immunotherapy on antibody-producing cells and thus on levels of pathogenic autoantibodies is insufficient. Therefore, therapeutic response is sometimes prolonged with necessity of long-time intensive care treatment and also irreversible deficits occur in severe cases. This trial will investigate the efficacy and safety of bortezomib, a proteasome inhibitor known to selectively deplete plasma cells, in patients with severe autoimmune encephalitis who have been treated with rituximab with insufficient response.. Generate-Boost is an investigator-initiated, multicenter, double-blinded, randomized controlled phase II trial which will be conducted in specialized neurological hospitals within the GENERATE (GErman NEtwork for Research on AuToimmune Encephalitis) network in Germany. Adult patients with severe autoimmune encephalitis (modified Rankin scale, mRS ≥ 3), autoantibodies against neuronal surface antigens, and pretreatment with rituximab are eligible for study participation. Fifty patients will be randomized 1:1 and undergo up to 3 cycles (each 21 days with 4 s. c. applications) of bortezomib or placebo. All patients will receive concomitant medication with dexamethasone, acyclovir and co-trimoxazole. The primary efficacy endpoint is the mRS score 17 weeks after first treatment application. Secondary endpoints are neurocognitive function, antibody titers, markers of neuronal cell damage, length of ICU/hospital stay, and mRS and Glasgow coma scale scores throughout the trial up to week 17. General and bortezomib-specific adverse events are monitored continuously.. The expected outcome of the study is to obtain first reliable data on a hypothesis-driven therapeutic option in severe and difficult-to-treat autoimmune encephalitis. If treatment with bortezomib is beneficial in these cases, this will be the basis for implementation in the current guidelines.. Clinicaltrials.gov , NCT03993262 . Registered June 20, 2019; German Clinical Trials Register, DRKS00017497.

Topics: Acyclovir; Adult; Autoantibodies; Bortezomib; Clinical Trials, Phase II as Topic; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Encephalitis; Germany; Glasgow Coma Scale; Hashimoto Disease; Humans; Immunotherapy; Multicenter Studies as Topic; Prospective Studies; Proteasome Inhibitors; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We assessed the incidence and determinants of bacteremia, pneumonia, and sinusitis/otitis in HIV-positive people receiving cotrimoxazole (CTX) or dapsone-pyrimethamine (DP) for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) within a randomized clinical trial. In total, 244 patients were randomized: 122 were assigned to CTX and 122 to DP. In the cohort, 22 bacteremia, 63 pneumonia, and 39 sinusitis/otitis cases were observed. Incidence rates of bacteremia, pneumonia, and sinusitis/otitis as well as the 2-year probability of remaining free from any bacterial infection were not significantly different between the two groups. At multivariate analysis, the risks of developing bacteremia and pneumonia were found to be independently increased by the use of a central venous catheter (hazard ratio [HR], 4.48; p <.05 and HR, 4.13; p <.01, respectively) and by hospitalization (HR, 28.82; p <.05 and HR, 10.15; p <.05, respectively). In conclusion, CTX at the dosage employed for primary PCP/TE prophylaxis does not seem to protect against bacterial infections more than second-line DP.

Topics: Adult; Animals; Anti-Infective Agents; Bacterial Infections; Dapsone; Encephalitis; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Pneumocystis; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the influence of the dose of co-trimoxazole prophylaxis on the risk of toxoplasmosis in human immunodeficiency virus (HIV)-infected patients, we performed a nested case-control study of 32 patients with toxoplasmosis (case patients) and 64 patients without toxoplasmosis (control patients) who were matched by CD4 cell count and Toxoplasma gondii serostatus; these patients were from a cohort of 521 HIV-infected patients who underwent a diagnostic neuroimaging study between March 1993 and January 1997. Twenty-seven (84.4%) of 32 case patients and 33 (51.6%) of 64 control patients received low doses of co-trimoxazole, a finding associated with an adjusted odds ratio (OR) of 9.36 (95% confidence interval [CI], 2.05-42.75) and indicating 89% protective efficacy for high doses. Fifteen (46.9%) of 32 case patients and 16 (25%) of 64 control patients were exposed to rifampin (adjusted OR, 3.38; 95% CI, 1.08-10.61). These results indicate that high doses of co-trimoxazole appear to be more effective than low doses for lowering the risk of toxoplasmosis in HIV-infected patients and that rifampin therapy may reduce the efficacy of co-trimoxazole.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Antibiotics, Antitubercular; Case-Control Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Encephalitis; Female; HIV Infections; Humans; Male; Rifampin; Toxoplasma; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The aim of the present pilot study was to compare the efficacy and safety of trimethoprim (TMP) and sulfamethoxazole (SMX) with those of the standard therapy pyrimethamine (P)-sulfadiazine (S) for the treatment of toxoplasmic encephalitis in patients with AIDS. This was a pilot, multicenter, randomized, and prospective study. Patients were randomly assigned to receive TMP (10 mg/kg of body weight/day) and SMX (50 mg/kg/day) or P (50 mg daily) and S (60 mg/kg/day) as acute therapy (for 4 weeks) and then as maintenance therapy for 3 months at half of the original dosage. Seventy-seven patients were enrolled and randomized to the study: 40 patients were treated with TMP-SMX and 37 were treated with P-S. There was no statistically significant difference in clinical efficacy during acute therapy. In contrast, patients randomized to TMP-SMX appeared more likely to achieve a complete radiologic response after acute therapy. Adverse reactions were significantly more frequent in patients treated with P-S, and skin rash was the most common adverse event noted in these patients. In conclusion, the results of the study suggest that TMP-SMX appears to be a valuable alternative to P-S, in particular in patients with opportunistic bacterial infections.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Encephalitis; Female; Humans; Male; Pilot Projects; Prospective Studies; Pyrimethamine; Sulfadiazine; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Encephalitis; Humans; Pyrimethamine; Randomized Controlled Trials as Topic; Sulfadiazine; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the efficacy and safety of three regimens for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) and to evaluate their effect on survival in patients with HIV infection.. Randomized, open label, prospective trial.. A single Infectious Diseases Department in Italy.. HIV-infected patients (n = 197) with a CD4 count < 200 x 10(6)/l and without previous PCP or TE.. Patients were randomly assigned to receive (1) aerosolized pentamidine (AP; 300 mg monthly), (2) cotrimoxazole (CTX; 160 mg trimethoprim and 800 mg sulfamethoxazole every other day), or (3) dapsone-pyrimethamine (DP; 100 mg weekly dapsone and 25 mg biweekly pyrimethamine).. PCP, TE, death, and drug-limiting toxicity. Considering difference in PCP occurrence the trial was interrupted on June 1992. Observation was prolonged until June 1994 for TE and survival.. Intention-to-treat analysis yielded PCP rates of 10.2 per 100 person-years in the AP, 2.0 in the CTX, and 32.1 in the DP group [adjusted relative risk of DP versus CTX: 17.5; 95% confidence interval (CI), 2.2-139.6; P = 0.007]. TE rates in patients with positive Toxoplasma serology were 25.6 per 100 person-years in the AP, 8.9 in the CTX and 9.4 in the DP group. In 'on treatment' analysis, no episode of TE developed in the DP group, and rates were 34.7 per 100 person-years in the AP and 2.5 in the CTX group (AP versus CTX: P = 0.01; AP versus DP: P = 0.004). The adjusted risk of mortality for the DP group was 2.8 times that of the CTX group in the first part of the study (95% CI, 1.1-7.3; P = 0.037), and 1.8 times (95% CI, 1.1-2.9; P = 0.02) in the prolonged follow-up. No significant difference in the occurrence of serious adverse reactions was observed between the three treatment groups.. Intermittent CTX was more effective than low-dose DP and showed a slight but not significant advantage on AP for primary PCP prophylaxis. DP was associated with a shorter survival. Both CTX and DP resulted in a significant reduction in the risk of TE.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Dapsone; Encephalitis; Female; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Twenty-four consecutive HIV-positive patients affected by Toxoplasma gondii encephalitis received trimethoprim-sulfamethoxazole (cotrimoxazole) as acute-phase treatment. Two dosage regimens of cotrimoxazole were used: 40 mg/kg/day (12 patients) or 120 mg/kg/day (12 patients) of total compound (trimethoprim plus sulfamethoxazole). Clinical and radiological responses to treatment were evaluated, and the product-limit method for survival data analysis was used. Eighteen of 24 patients showed both a clinical and radiological response (75% response rate). There were no differences in response rates between patients receiving the two dosage regimens of cotrimoxazole. Adverse reaction consisted of leukopenia (two cases) and skin rash (three cases) which led to the discontinuation of the drug in one case. These results suggest that a randomized, controlled clinical trial should be carried out comparing cotrimoxazole versus sulfadiazine-pyrimethamine in AIDS patients with Toxoplasma gondii encephalitis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Drug Eruptions; Encephalitis; Female; Humans; Leukopenia; Male; Middle Aged; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Primary Whipple disease of the Central Nervous System is a rare entity whose outcome might be fatal if not promptly diagnosed and treated. Few cases are reported in the literature with heterogeneous clinical and radiological presentations which often make the diagnosis extremely challenging. We report a case of primary Whipple disease of the Central Nervous System presenting with rhombencephalitis in a female patient in immunosuppressive treatment for rheumatoid arthritis. We describe the management of our patient and discuss the features of this rare clinical entity.

Topics: Aged; Anti-Bacterial Agents; Central Nervous System; Encephalitis; Female; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Whipple Disease

Acanthamoeba spp. is a free-living amoeba, frequently involved in keratitis by contact lens in immunocompetent hosts. Anecdotal reports associate Acanthamoeba spp. as a cause of severe granulomatous encephalitis in immunocompromised and, less frequently, in immunocompetent subjects. Data regarding clinical and therapeutic management are scanty and no defined therapeutic guidelines are available. We describe an unusual case of non-granulomatous Acanthamoeba cerebellitis in an immunocompetent adult male, with abrupt onset of neurological impairment, subtle hemorrhagic infarction at magnetic resonance imaging, and initial suspicion of cerebellar neoplasm. Histopathological findings of excised cerebellar mass revealed the presence of necrosis and inflammation with structure resembling amoebic trophozoites, but without granulomas. Polymerase chain reaction from cerebellar tissue was positive for Acanthamoeba T4 genotype. Due to gastrointestinal intolerance to miltefosine, the patient was treated with long-term course of fluconazole and trimethoprim/sulphamethoxazole, obtaining complete clinical and neuroradiological resolution.

Topics: Acanthamoeba; Adult; Amebiasis; Antiprotozoal Agents; Cerebellum; Dominican Republic; Encephalitis; Fluconazole; Humans; Italy; Male; Polymerase Chain Reaction; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Cortex Hormones; Ampicillin; Encephalitis; Female; Humans; Magnetic Resonance Imaging; Rhombencephalon; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Although it is an orphan disease, isolated central nervous system Whipple's disease is one of the "must be known" conditions in neurology because it belongs to the list of "treatable disorders". Here, we present two cases which highlight the importance of early diagnosis. Additionally, we provide a discussion on up to date diagnostic approach to this life-threatening disorder.

Topics: Adult; Anti-Bacterial Agents; Ataxia; Ceftriaxone; Central Nervous System Infections; Encephalitis; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Whipple Disease

The objective of this study is to characterize the common risk factors, clinical presentation, imaging findings, treatment and outcome of nocardial infection.. A retrospective cohort study. We reviewed the charts of all patients with nocardiosis in the Chaim Sheba Medical Center, a tertiary medical center in Israel, between the years 1996 and 2011.. A total of 39 patients who had positive culture of Nocardia were analyzed. The majority of our patients were immunocompromised (74.5%), mostly due to corticosteroid therapy. None had HIV/AIDS. The clinical presentation was either acute or a chronic smoldering illness. The three major clinical syndromes were pleuropulmonary, neurological and skin/soft tissue infection about 20.5% each. Pathology in the lungs was seen in most of the patients by CT scan; discrete nodules and wedge shaped pleural based consolidations were the most frequent findings. Brain lesions consistent with abscesses were detected in 10 patients by brain imaging. Some cases had relapsing disease in spite of antimicrobial treatment. 25% of examined isolates were resistant to trimethoprim/sulfamethoxazole. The duration of intravenous antimicrobial treatment ranged from one month to over a year in the severe cases. One year mortality rate was 32%.. Nocardiosis requires a high clinical index of suspicion in order to diagnose and treat promptly. Disease extent and bacterial susceptibility have important implications for prognosis and treatment.

Topics: Adrenal Cortex Hormones; Adult; Aged; Amikacin; Carbapenems; Ceftriaxone; Cohort Studies; Encephalitis; Female; Humans; Immunocompromised Host; Israel; Male; Middle Aged; Nocardia Infections; Pleuropneumonia; Retrospective Studies; Risk Factors; Skin Diseases, Bacterial; Soft Tissue Infections; Tertiary Care Centers; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Neurobrucellosis is an uncommon complication of pediatric brucellosis. Acute meningitis and encephalitis are the most common clinical manifestations, however symptoms may be protean and diagnosis requires a high index of suspicion in patients from endemic areas. Diagnosis is often based on neurological symptoms, serology, and suggestive brain imaging because cerebrospinal fluid culture yields are low. Two cases of pediatric neurobrucellosis with unusual clinical and radiologic findings are presented.

Topics: Adolescent; Anti-Bacterial Agents; Brucellosis; Child; Doxycycline; Drug Therapy, Combination; Encephalitis; Female; Gentamicins; Humans; Incidence; Israel; Meningitis; Neuroimaging; Rifampin; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Isolated Whipple disease of the central nervous system is a rare occurrence. Migratory arthralgias and gastrointestinal problems, including malabsorption, abdominal pain, diarrhea, and weight loss, are common presenting symptoms.. For those patients with systemic signs and symptoms of Whipple disease, 6% to 43% will have clinically manifested CNS involvement that may include alterations in personality, ataxia, and dementia. We report our experience with a patient, who was successfully treated for Whipple disease 12 years prior to presentation and had a magnetic resonance image of the brain that revealed two solitary lesions resembling a tumor upon presentation.

Topics: Anti-Infective Agents; Brain Neoplasms; Chronic Disease; Consciousness Disorders; Diagnosis, Differential; Diagnostic Errors; Encephalitis; Headache; Humans; Hypothalamus; Magnetic Resonance Imaging; Male; Middle Aged; Neurosurgical Procedures; Temporal Lobe; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tropheryma; Whipple Disease

Topics: Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Costs and Cost Analysis; Encephalitis; HIV Infections; Humans; Safety; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

We describe a case of breakthrough cerebral toxoplasmosis during atovaquone therapy in a child who was intolerant of conventional prophylactic regimens after hematopoietic stem cell transplantation. The available data on the efficacy of atovaquone prophylaxis in Toxoplasma sero-positive stem cell transplant recipients remain limited, and other strategies, such as preemptive strategy using toxoplasma PCR or TMP-SMX desensitization should be considered in this setting.

Topics: Anti-Infective Agents; Atovaquone; Child; Encephalitis; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Time Factors; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

A case-control study to identify the risk factors for toxoplasmic encephalitis (TE) among HIV-infected patients with latent Toxoplasma gondii infection was performed in a teaching hospital in south-eastern Brazil. Although the subjects were all positive for serum IgG antibodies to Toxoplasma, some (the cases) developed TE during routine follow-up at the hospital whereas others (the controls) did not. Adjusted odds ratios (aOR) were estimated by multiple logistic regression after controlling for potential confounders. Only 46 (22%) of the 210 cases but 93 (45%) of the 205 controls were on prophylactic regimens with co-trimoxazole [aOR = 0.30; 95% confidence interval (CI) = 0.15-0.60]. Subjects with fewer than 100 (aOR = 37.09; CI =7.49-183.67) or between 100 and 200 CD4 cells/microl (aOR = 10.20; CI =2.00-51.90) were at substantially increased risk of developing TE than those with >400 CD4 cells/microl. Although the results of preliminary, unadjusted data analysis indicated that male sex and homosexual or bisexual activity might be additional risk factors, these associations were not found to be statistically significant by multiple regression analysis. In conclusion, no risk factors for TE other than low CD4 cell counts and failure to receive prophylaxis were found among HIV-infected Brazilian patients with past exposure to Toxoplasma. Seropositive patients with CD4 cell counts above 100/microl (the point at which specific prophylaxis is usually recommended) but below 200/microl might also benefit from effective anti-TE prophylaxis.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibiotic Prophylaxis; Case-Control Studies; CD4 Lymphocyte Count; Encephalitis; Female; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Statistics as Topic; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

The spontaneous secretion in vitro of anti-Toxoplasma gondii antibodies by peripheral blood mononuclear cells was assessed in 69 patients with AIDS-related brain lesions. The sensitivity and specificity of this assay in the diagnosis of toxoplasmic encephalitis (TE) were found to be 85.4% and 92.8%, respectively. Twenty-four patients with TE were observed during 1-year follow-up after initiation of anti-Toxoplasma treatment and classified on the basis of their clinical and radiologic responses as sustained responders (SR; n = 11), incomplete responders (IR; n = 7) or transient responders (TR; n = 6). In vitro anti-T. gondii antibody secretion decreased as early as the first month after initiation of treatment and disappeared within the year in SRs, persisted in IRs, and decreased but rebounded at relapse in the TR patients. In vitro anti-T. gondii antibody, which reflects immune system activation by parasitic antigens, could be a surrogate marker of TE in AIDS patients.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Antibodies, Protozoan; Antiprotozoal Agents; Encephalitis; France; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Pyrimethamine; Retrospective Studies; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Research results to determine the best prophylactic regimen for Pneumocystis carinii pneumonia (PCP) are reported. Overall results from these studies indicate patients who are eligible for PCP prophylaxis should be advised to take double-strength trimethoprim/sulfamethoxazole (TMP/SMX) on a daily basis, a dosage found more effective than thrice-weekly. To handle problems with side effects, one study demonstrated the success of using a 6-day dose escalation method that allowed 80 percent of the participants to complete treatment for 6 months. Patients remaining intolerant to TMP/SMX have the options of using atovaquone (not yet FDA-approved for PCP prophylaxis) or aerosolized pentamidine (not approved for treatment of PCP), which have been shown to be safe and effective in PCP prophylaxis. Due to recent FDA reforms, the use of off-label drugs may increase, but patients and physicians are cautioned that problems with insurance reimbursement may develop.

Topics: Aerosols; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; CD4 Lymphocyte Count; Clinical Trials as Topic; Dapsone; Drug Administration Schedule; Encephalitis; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

In France, where 70% of adults are latently infected by toxoplasma, from 20% to 40% of patients with AIDS developed toxoplasmic encephalitis until recently. The prophylactic use of drugs which are active against pneumocystis and toxoplasma has proven to be efficient. These drugs are trimethoprim-sulfamethoxazole or dapsone-pyrimethamine. With the extent of these primary prophylaxis, there is a decrease of risk of toxoplasma encephalitis; thus the rate of toxoplasma encephalitis among opportunistic infections has fallen off from 19% of the patients in 1988 to 6% in 1994, in the department of infectious diseases of the Pitié-Salpêtrière hospital. However, toxoplasmic abscesses occurring despite the prophylaxis are frequently slow growing lesions which can become huge with a moderate mass effect, mimicking the pattern of primary cerebral lymphoma. The rule of antitoxoplasmic trial treatment must be strictly followed, even under prophylaxis.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiprotozoal Agents; Brain Abscess; Brain Neoplasms; Chemoprevention; Dapsone; Diagnosis, Differential; Drug Combinations; Encephalitis; France; Humans; Lymphoma, AIDS-Related; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Encephalitis; Female; Humans; Male; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

We report the case of a 57-year-old man with Listeria rhombencephalitis. This had been ascertained by means of Listeria isolation from the cerebrospinal fluid. After an nonspecific prodromial period with nausea and headache, he developed fever, meningism, brain stem dysfunction and an organic psychosis. With early antibiotic therapy (ampicillin/gentamycin), it was possible to bring about a restitio ad integrum. Different brain-imaging methods (computed tomography, MRI, brain SPECT) in the acute and follow-up stages are discussed.

Topics: Ampicillin; Drug Therapy, Combination; Encephalitis; Follow-Up Studies; Gentamicins; Humans; Listeria monocytogenes; Listeriosis; Magnetic Resonance Imaging; Male; Middle Aged; Neurocognitive Disorders; Neurologic Examination; Rhombencephalon; Tomography, Emission-Computed, Single-Photon; Trimethoprim, Sulfamethoxazole Drug Combination

To study Toxoplasma encephalitis (TE) in advanced HIV infection, including predictive factors, possible prophylactic regimens and impact on survival.. Epidemiological analysis of data collected prospectively during the Alpha study, a double-blind, randomized clinical trial, comparing two doses of dideoxyinosine in patients with advanced HIV disease.. First episode of TE occurred in 75 out of 499 patients participating in the trial.. Kaplan-Meier estimates and semi-parametric Cox's model were used.. A low CD4 cell count and a positive Toxoplasma serology were strongly predictive of the occurrence of TE. In patients with CD4 counts < 100 x 10(6)/l and a positive Toxoplasma serology at entry to the study, the 12-month TE incidence was 25.4%. Patients who were receiving at entry any of the following potentially antitoxoplasmic drugs: trimethoprim-sulphamethoxazole, pyrimethamine, dapsone, pyrimethamine-sulphadoxine or sulphadiazine, had a lower TE incidence than those who were not; 6.2 versus 18.8%, respectively (P < 0.001). The rate of survival 12 months after TE was 29.6%. Even after adjusting the major prognostic covariates, TE was predictive of death (P < 0.001; relative risk, 1.8).. The high HIV incidence, morbidity and mortality in high-prevalence areas suggests that primary prophylaxis should be given in patients at high risk for toxoplasmic reactivation.

Topics: Adult; AIDS-Related Opportunistic Infections; Dapsone; Encephalitis; Female; Humans; Male; Middle Aged; Pyrimethamine; Sulfadiazine; Sulfadoxine; Survival Rate; Toxoplasmosis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the efficacy of low-dose trimethoprim-sulfamethoxazole (trimethoprim, 160 mg plus sulfamethoxazole, 800 mg; one tablet twice daily, 2 days per week) as primary prophylaxis against toxoplasmic encephalitis in patients with human immunodeficiency virus (HIV) infection and previous Pneumocystis carinii pneumonia.. A retrospective study.. Tertiary referral teaching hospital.. During a 3-year period after primary episodes of P. carinii pneumonia, 60 patients received trimethoprim-sulfamethoxazole, and 95 patients received pentamidine (aerosolized in 78 patients and intravenous in 17 patients) as secondary prophylaxis.. No patient in the trimethoprim-sulfamethoxazole group and no patient seronegative for Toxoplasma gondii developed toxoplasmic encephalitis, compared with 12 of 36 (33%; 95% Cl, 19% to 51%) seropositive patients in the pentamidine group (trimethoprim-sulfamethoxazole compared with pentamidine, P = 0.008). A significant difference was seen in the time to development of toxoplasmic encephalitis between the trimethoprim-sulfamethoxazole group (no case at 1153 days) and the pentamidine group (median time, 460 days) (P = 0.004). Neither the CD4+ lymphocyte count at the start of prophylaxis nor zidovudine therapy during the period of prophylaxis influenced the rate of toxoplasmic encephalitis in any group.. Low-dose trimethoprim-sulfamethoxazole (four tablets per week) appears to be effective prophylaxis against toxoplasmic encephalitis in HIV-infected patients with previous P. carinii pneumonia. A prospective, randomized, controlled study is needed to further evaluate these findings.

Topics: Acquired Immunodeficiency Syndrome; Animals; Antibodies, Protozoan; CD4-Positive T-Lymphocytes; Encephalitis; Follow-Up Studies; Humans; Immunoglobulin G; Leukocyte Count; Male; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Encephalitis; Humans; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

A 14 year old boy developed the syndrome of Bickerstaff's brainstem encephalitis during the course of bacteriologically proved typhoid fever. The clinical course and the results of various neurological investigations are detailed. This report adds a further manifestation to the published neuropsychiatric complications of typhoid fever.

Topics: Adolescent; Ampicillin; Drug Therapy, Combination; Electroencephalography; Encephalitis; Humans; Male; Salmonella typhi; Trimethoprim, Sulfamethoxazole Drug Combination; Typhoid Fever

The aim of this retrospective study was to define a diagnostic strategy and to evaluate the efficacy of cotrimoxazole (CTMX) for presumed cerebral toxoplasmosis in patients with AIDS. Twelve patients with toxoplasma encephalitis were reviewed. The best diagnostical signs of reactivated acute cerebral toxoplasmosis were the association of neurological symptoms indicative of focal cerebral lesions, and a radiological picture showing ring contrast enhanced hypodense mass-lesions; serology was unreliable for the diagnosis. Five patients out of twelve were treated without delay and until death with CTMX. Only these improved their clinical and radiological status obviously. Moreover, their median survival time was clearly longer (160 days, versus 9 days) and their autopsy demonstrated the absence of active necrotizing lesions of toxoplasma encephalitis. So, CTMX seems to be an efficient therapy for suspected cerebral toxoplasmosis in AIDS. Nevertheless, further prospective randomized therapeutic trials are required to confirm this impression.

Topics: Acquired Immunodeficiency Syndrome; Adult; Encephalitis; Female; Humans; Male; Middle Aged; Retrospective Studies; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

There are increasing reports of citrobacter central nervous system infections in neonates. These organisms cause brain abcesses in a high percentage of patients. They may be resistant to commonly used antibiotics. We report a term male infant with underlying meningo-myelocoele and hydrocephalus in whom Citrobacter diversus meningitis and ventriculitis developed. Initial antibiotic therapy including intraventricular amikacin failed to sterilize the ventricles or alter a deteriorating clinical course. Adding intravenous trimethoprim-sulfamethoxazole to the therapeutic regimen resulted in reversal of a progressively worsening condition and eventual recovery. Trimethoprim-sulfamethoxazole should be considered as a potentially useful alternative antibiotic for susceptible central nervous system infections.

Topics: Amikacin; Cerebral Ventricles; Citrobacter; Drug Combinations; Encephalitis; Enterobacteriaceae Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Meningitis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination